Arteriovenous catheterization will be performed in the dog to determine the effects of certain pharmacologic agents on the net production and degradation of plasma cAMP and cGMP across specific organs. Studies of plasma cyclic nucleotides in normals and patients with hyper tension will be done to investigate possible abnormalities in cyclic nucleotide metabolism. cGMP appears to be involved in the action of acetylcholine at muscarinic receptor sites. Further, studies in bovine superior cervical ganglion, canine thyroid, and human lymphocyte will be performed to investigate this relationship. An immunocytochemical technique for the localization of cyclic nucleotides will be used in brain tissues and other tissues to further identify the cellular localization of the nucleotides. This technique will be adapted for the ultrastructural localization of cGMP and cAMP. Studies on the role of cGMP in growth hormone secretion will be extended, as will those on the role of the cyclic nucleotides in adaptation to changes in pH. The principal investigator has developed sensitive radioimmunoassays for measuring cyclic uridine monophosphate (cUMP) and cyclic inosine monophosphate (cIMP), and these assays will be used to investigate whether these nucleotides are present in mammalian tissues and whether they have physiologic roles.